Hydrocortisone for Term Hypotension

Hydrocortisone Treatment of Cardiovascular Insufficiency in Term and Late Preterm Infants: A Randomized Controlled Trial

This trial will evaluate the effects of a 7-day course of hydrocortisone therapy on short-term morbidity, cardiovascular function, long-term neurodevelopment, and mortality in critically ill, term and late preterm infants diagnosed with cardiovascular insufficiency as defined by a need for inotrope therapy in the first 72 hours of age.

Study Overview

• Status: Completed
• Conditions: Infant, Newborn, Diseases; Cardiovascular Insufficiency
• Intervention / Treatment: Drug: Hydrocortisone; Drug: Placebo

Detailed Description

Cardiovascular insufficiency is common and potentially life-threatening in critically ill term and late preterm newborns admitted to the newborn intensive care unit (NICU) in the first few days of age.

This study proposes to conduct a multicenter, randomized, masked, placebo-controlled trial within the Neonatal Research Network (NRN). This trial will evaluate the effects of a 7-day course of hydrocortisone therapy on short-term morbidity, cardiovascular function, long-term neurodevelopment, and mortality in critically ill, term and late preterm infants diagnosed with cardiovascular insufficiency as defined by a need for inotrope therapy in the first 72 hours of age.

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • University of Alabama at Birmingham
  • California
    • Los Angeles, California, United States, 90025
      • University of California - Los Angeles
    • Palo Alto, California, United States, 94304
      • Stanford University
  • Georgia
    • Atlanta, Georgia, United States, 30303
      • Emory University
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Wayne State University
  • Missouri
    • Kansas City, Missouri, United States, 64108
      • Children's Mercy Hospital
  • New Mexico
    • Albuquerque, New Mexico, United States, 87131
      • University of New Mexico
  • New York
    • Rochester, New York, United States, 14642
      • University of Rochester
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University
    • Durham, North Carolina, United States, 27705
      • RTI International
  • Ohio
    • Cincinnati, Ohio, United States, 45267
      • Cincinnati Children's Medical Center
    • Cleveland, Ohio, United States, 44106
      • Case Western Reserve University
    • Columbus, Ohio, United States, 43205
      • Research Institute at Nationwide Children's Hospital
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania
  • Texas
    • Dallas, Texas, United States, 75235
      • University Of Texas Southwestern Medical Center At Dallas
    • Houston, Texas, United States, 77030
      • University of Texas Health Science Center at Houston

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 7 months and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Gestational age greater than or equal to 34 weeks at birth
• Admitted to the center NICU by 48 hours of age
• Intubated and mechanically ventilated for a minimum of 2 hours before 72 hours postnatal age

Exclusion Criteria:

• Receiving ECMO
• Intubated for the sole purpose of anticipated surgery or airway anomalies
• Treatment will be limited based on poor prognosis
• Receiving dexamethasone or hydrocortisone
• Receiving ibuprofen or indomethacin
• Congenital heart disease
• Hypotension thought to result from specific, immediately remediable factors including placental hemorrhage, acute hemorrhage or tension pneumothorax
• Pituitary hypoplasia or congenital adrenal hyperplasia
• Any chromosomal disorder
• Hypertension in the absence of inotrope therapy as defined by mean arterial blood pressure > 95th percentile
• Initiation of whole body cooling for moderate or severe neonatal encephalopathy
• Brain disorders or any other known structural abnormality
• Major anomalies

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Saline placebo	Drug: Placebo; 7 days of intravenous or intramuscular placebo (normal saline in equal volume) 1 mg/kg loading dose x 1; 0.5 mg/kg q 6 hours x 12 doses; 0.5 mg/kg q 12 hours x 4 doses; 0.5 mg/kg q day x 1 dose
Active Comparator: Hydrocortisone; hydrocortisone (hydrocortisone sodium succinate, plain; will not have benzyl alcohol) given through intravenous line or by intramuscular injection if no intravenous line	Drug: Hydrocortisone; • 7 day course of hydrocortisone (hydrocortisone sodium succinate, plain; will not have benzyl alcohol) given through intravenous line or by intramuscular injection if no intravenous line). 1 mg/kg loading dose x 1; 0.5 mg/kg q 6 hours x 12 doses; 0.5 mg/kg q 12 hours x 4 doses; 0.5 mg/kg q day x 1 dose

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Death	This is measured as Yes if an infant died between birth and 22-26 months corrected gestational age; Otherwise, No.	Birth to 22-26 months corrected gestational age
Number of Participants With Neurodevelopmental Impairment	This is measured as Yes if an any hearing impairment or visual impairment is noted, if non-normal gross motor function level is noted, any seizures have been noted, or if the cognitive, language, or motor scores of the Bayley III score are more than 1 standard deviation below the average; Otherwise, No.	Birth to 22-26 months corrected gestational age
Number of Participants With Death or Neurodevelopmental Impairment	A composite outcome that measures the occurrence of death or neurodevelomental impairment between birth and 22-26 months corrected gestational age.	Birth to 22-26 months corrected gestational age

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of Mechanical Ventilation	This is measured as the number of days between birth and 60 days of life of mechanical ventialtion of laryngeal intubation.	Birth to 60 days of life
Days to Full Feeds	The day of life at which full nipple feeds were reached between birth and 60 days of life. Full nipple feeds are defined as at least 120 mg/kg/day.	Birth to 60 days of life
Number of Participants With Need for Gastronomy Tube	This is measured as Yes if a gastronomy tube was placed anytime prior to final status between birth and 60 days of life; Otherwise, No	Birth to 60 days of life
Duration of Oxygen Requirement	This is measured as the number of days between birth and 60 days of life that an infant was on oxygen in the hospital.	Birth to 60 days of life
Number of Participants With Need for Home Oxygen	This is measured as Yes if an infant was discharged to home while on oxygen between birth and 60 days of life; Otherwise, No.	Birth to 60 days of life
Hospital Length of Stay	This is measured as the number of days between birth and 60 days of life that an infant was in the hospital. Infants who died or transferred to another care facility were not included.	Birth to 60 days of life
Number of Participants With Renal Insufficiency	This is measured as Yes if an infant had renal insufficieny between birth and 60 days of life; Otherwise, No. Renal insufficiency is defined as creatinine less than 2 during 7 days after first treatment	Birth to 60 days of life
Number of Participants With Necrotizing Enterocolitis	This is measured as Yes if an infant necrotizing enterocolitis (NEC) between birth and 60 days of life; Otherwise, No. NEC could be proven with or without surgery	Birth to 60 days of life
Number of Participants With Need for ECMO Therapy	This is measured as Yes if an infant received ECMO treatment anytime between birth and 60 days of life; Otherwise, No. Extracorporeal membrane oxygenation (ECMO) is a treatment that uses a pump to circulate blood through an artificial lung back into the bloodstream of a very ill baby.	Birth to 60 days of life
Number of Participants With Inotrope Exposure	This is measured as Yes if an infant was receiving inotropes on the specific day after the initiation of study drug.	24 hours prior to study drug administration through 3 days post study drug administration.
Inotrope Duration	This is calculated as the number of days on inotropes starting 24 hours prior to initiation of study drug, during the 7-day study drug administration period, and for 3 days after the study drug.	24 hours prior to study drug administration through 3 days post study drug administration.
Maximum Inotrope Dose	This is calculated as the maximum dose of all inotropes in the 10 days following the initiation of study drug administration. For the purposes of this calculation, dopamine and dobutamine doses were considered equivalent and 0.01 mcg/kg/min of epinephrine was equal to 5 mcg/kg/min of dopamine.	From start of study drug administration (7 days) through 3 days post study drug administration.
Oxygenation Index	This is calculated as fraction of inspired oxygen (FiO2), as a percentage, multiplied by the mean airway pressure divided by partial pressure of oxygen in arterial blood (PaO2), during study drug administration. A lower oxygenation index is better.	Birth to 60 days of life
Respiratory Severity	This is calculated as fraction of inspired oxygen (FiO2), as a percentage, multiplied by the mean airway pressure during study drug administration. Higher score means more severe.	Birth to 60 days of life
Number of Participants With Fluid Boluses Given	This is measured as Yes if an infant received fluid boluses anytime before or during study drug administration between birth and 60 days of life; Otherwise, No.	Birth to 60 days of life
Number of Boluses Given	The number of fluid boluses given per participant, if any, before or during study drug administration between birth and 60 days of life	Birth to 60 days of life

Collaborators and Investigators

• Sponsor: NICHD Neonatal Research Network
• Collaborators: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD); National Center for Research Resources (NCRR)
• Investigators: Principal Investigator: Kathleen A Kennedy, MD, MPH, The University of Texas Health Science Center, Houston; Principal Investigator: Barbara J Stoll, MD, Emory University; Principal Investigator: Brenda B Poindexter, MD, MS, Indiana University; Principal Investigator: Ron N Goldberg, MD, Duke University; Principal Investigator: Edward F Bell, MD, Michele C Walsh, MD Study Principal Investigator Case Western Reserve University, Rainbow Babies and Children's Hospital Seetha Shankaran, MD Study Principal Investigator Wayne State University Abbot R Laptook, MD Study Principal Investigator Brown Un; Study Chair: Erika Fernandez, MD, University of New Mexico; Principal Investigator: Myra Wycoff, MD, University of Texas, Southwestern Medical Center at Dallas

Publications and helpful links

Helpful Links

• NICHD Neonatal Research Network site
• NICHD Pregnancy & Perinatology Branch

Study record dates

Study Major Dates

• Study Start (Actual): June 19, 2014
• Primary Completion (Actual): March 20, 2018
• Study Completion (Actual): March 20, 2018

Study Registration Dates

• First Submitted: September 26, 2013
• First Submitted That Met QC Criteria: September 26, 2013
• First Posted (Estimate): October 1, 2013

Study Record Updates

• Last Update Posted (Actual): July 6, 2021
• Last Update Submitted That Met QC Criteria: July 2, 2021
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Keywords: Intubation; Mechanical ventilation; NICHD Neonatal Research Network; Neurodevelopmental impairment
• Additional Relevant MeSH Terms: Infant, Newborn, Diseases; Anti-Inflammatory Agents; Hydrocortisone
• Other Study ID Numbers: NICHD-NRN-0052; U10HD036790 (U.S. NIH Grant/Contract); U10HD021364 (U.S. NIH Grant/Contract); U10HD021373 (U.S. NIH Grant/Contract); U10HD021385 (U.S. NIH Grant/Contract); U10HD027851 (U.S. NIH Grant/Contract); U10HD027853 (U.S. NIH Grant/Contract); U10HD027856 (U.S. NIH Grant/Contract); U10HD027880 (U.S. NIH Grant/Contract); U10HD027904 (U.S. NIH Grant/Contract); U10HD034216 (U.S. NIH Grant/Contract); U10HD040492 (U.S. NIH Grant/Contract); U10HD040689 (U.S. NIH Grant/Contract); U10HD053109 (U.S. NIH Grant/Contract); U10HD040461 (U.S. NIH Grant/Contract); U10HD068244 (U.S. NIH Grant/Contract); U10HD068263 (U.S. NIH Grant/Contract); U10HD068270 (U.S. NIH Grant/Contract); U10HD068278 (U.S. NIH Grant/Contract); U10HD068284 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO